CHM113A: General Chemistry

D r. Pa r t h as ara thi Su b r a ma n ian

D e pa rtment of C he mis try

IIT K a n p u r
p a r t h as @iitk.ac.in

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 Cis-1,4-tert-Butylcyclohexane

• The most stable conformation of

cis-1,4-di-tert-butylcyclohexane is
the twist boat.

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 Why do We Study Conformations?
• Conformations will help us understand stability of a molecule
• Conformations can dictate reactivity.

• Let’s draw the conformations of cyclohexane derivative 1.

most stable conformation

 Conformations Influence Reactivity
• What about the compound 2?.

• Let’s draw the conformations of cyclohexane derivative 2.

• Both similar in energy so there is no significant preference for one over the other

• No possibility of epoxide formation from either of these conformations!

 Conformations Influence Reactivity
• 2-Aminocyclohexanols also exhibit such conformation dependent reactivity.

– trans-2-Aminocyclohexanol affords cyclopentane carboxaldehyde as the major

product

– cis-2-Aminocyclohexanol affords an ~1:1 mixture of cyclopentane

carboxaldehyde and cyclohexanone
 Conformations Influence Reactivity
• trans-2-Aminocyclohexanol has a preferred major conformation wherein both
substituents are equatorial
 Conformations Influence Reactivity
• cis-2-Aminocyclohexanols has two conformations both of which have one substituent
in the equatorial position and the other in axial position.
 Bicyclic systems-Decalins
• Decalins are fused bicyclic compounds (10
carbon atoms) wherein the ring junctions
can be either cis- or trans.

• In cis-decalin hydrogen atoms at the

bridgehead carbons are on the same face of
the rings

• In trans-decalin, the bridgehead hydrogens

are on opposite faces

• The six-membered rings in cis- and trans-

decalin assume chair conformations.

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 cis- and trans-decalins DO NOT interconvert

ring flip

3 syn-gauche butane intns’ contributes 3 X 0.9 kcal/mol, hence9

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cis-decalin is lesser stable by 2.7 kcal/mol than trans-decalin
Bicyclic Compounds - Decalin
 Bicyclic Compounds - Decalin
cis-Decalin can flip as the new structure would also have one axial and one equatorial
bond
1 3 2
2 4 3 4

3
4 1

2
1

1 2
4 4
3 4 3
3
2
2
1
1
Polycyclic Ring Systems

Cholesterol is a waxy steroid

found in the cell membranes. It
is an essential component of
mammalian cell membranes.

Corticosteroids: metabolism &

immune function
Anabolic Steroids: muscle &
bone growth
 Chair Conformations are Ubiquitous In Nature

• Consider glucose, a member of the carbohydrate family of biomolecules.

• Glucose exists almost entirely as its cyclic hemiacetal form.

• The Haworth projection, although widely used, may give the impression of the
ring being flat.
 Chair Conformations are Ubiquitous In Nature

• Glucose exists in the two forms shown below.

• The only difference in the two molecules is that the stereochemistry at the C1
carbon atom is different.
• Stereoisomeric molecules which differ in the configuration at only one stereogenic
center are called epimers.
 Epimers

• Epimers are stereoisomers that differ in the configuration at only one stereogenic
center.
• The carbon at which the stereochemistry differs is usually specified.

=>
 Epimers and Anomers
• Anomers are actually epimers that differ in configuration at the acetal/hemiacetal
carbon.
• This carbon atom is also referred to as the “anomeric carbon”.
• Two anomers of D-glucose are shown below.

• The hydroxyl group on the anomeric (hemiacetal) carbon is down (axial) in the
α anomer and up (equatorial) in the β anomer.
• The β anomer of glucose has all its substituents in equatorial positions.
• The hemiacetal carbon is called the anomeric carbon, easily identified as the
only carbon atom bonded to two oxygens.
 Does the a-anomer Exist in Significant Amount?

❑ Despite what we saw for cyclohexane (huge preference for the equatorial
position), the corresponding a-D-glucose is present in significantly higher ratio.

36% 64%

❑ The axial substituent in this case seems to be more stabilized compared to the
corresponding cyclohexanol.

11% 89%
 Anomeric Effect

• Alkyl substituents in cyclohexane prefer

equatorial position.

• Alkyl substituents in tetrahydropyran

prefer equatorial position.

• The anomeric carbon of the most

abundant natural sugar, D-
glucopyranose, also prefers the –OH
substituent in equatorial orientation.
36% 64%

• Making the substituent

more electronegative
rendered the axial
conformer more stable! 86% 14%
94% 06%
 Anomeric Effect

• Polarizability
• Orbital Overlap

dipole moment
cancels out

s*C-X s*C-X

• Overlap between lone pair dipole moment enhanced

• Overlap NOT possible
of oxygen and antibonding • Less dipole makes the
orbital of C-X possible molecule more stable
• As an extreme case, we can imagine complete donation of the lone pairs to give
the following resonance structure
 Evidence for Anomeric Effect

• The two C-Cl bonds in the molecule shown

are of different lengths, as indicated.

• Analysis of potential anomeric effect can provide the answer.

• Anomeric effect is
• operative for C-Cl

• A corresponding decrease in the C-O bond length is also observed.

 Stereoisomerism

• Isomers that have the same connectivity between atoms but different spatial
arrangement of their atoms are called stereoisomers.

• With rings and with C=C double bonds, cis-trans notation is used to distinguish
between stereoisomers

• Cis – Higher priority (CIP notation) groups are positioned on the SAME side of
a ring/double bond
• Trans – Higher priority (CIP notation) groups are positioned on OPPOSITE
sides of a ring/double bond

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 Stereoisomerism
• Optical Isomerism

• Optical isomers, or enantiomers, are mirror images of one another that don’t
superimpose on each other.
• Such entities are said to be chiral.
• Their properties of chiral chemicals differ from each other only when they interact
with other chiral entities (such as plane polarized light).

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 An Interesting Side-Note About Enantiomers

• How can we distinguish the following two enantiomers?

• There are more such enantiomeric pairs!

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 Chirality Associated with Tetrahedral Carbon Atom

• There can be many reasons for chirality to occur. We will discuss some of them.

• If a carbon atom is bonded to 4 unique groups of atoms, it results in chirality.

• Such a carbon atom is referred to being as “chiral”.

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 Achiral Carbon Atoms

• When the mirror image of an achiral structure is rotated, and the structures can be
aligned with each other, their mirror images are said to be superimposable.

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 Conformationally Mobile Systems
• Should the (cis)-1,2-dimethylcyclohexane chair conformation be chiral or achiral?
• It is not superimposable on its mirror image

Mirror
plane

• If enantiomers are in equilibrium with

each other through ring flipping, one
enantiomer cannot be separated from
the other.
• The freely interconverting mirror
images cancel out their optical
rotation, so it is achiral

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